Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values

A. Reum Kim, Kyu Sung Choi, Min Sung Kim, Kyung Min Kim, Ho Kang, Sojin Kim, Tamrin Chowdhury, Hyeon Jong Yu, Chae Eun Lee, Joo Ho Lee, Soon Tae Lee, Jae Kyung Won, Jin Wook Kim, Yong Hwy Kim, Tae Min Kim, Sung Hye Park, Seung Hong Choi, Eui Cheol Shin, Chul Kee Park

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures. Methods: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications. Results: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps. Conclusions: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.

Original languageEnglish
Pages (from-to)1995-2008
Number of pages14
JournalCancer Immunology, Immunotherapy
Volume70
Issue number7
DOIs
StateAccepted/In press - 2021

Keywords

  • High-grade glioma
  • Quantification
  • Radiomics
  • Tumor-associated macrophage
  • Tumor-infiltrating lymphocyte

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